scholarly journals Transforming growth factor–β in tissue fibrosis

2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Nikolaos G. Frangogiannis
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cellular Targets ◽  
Extracellular Matrix Molecules ◽  
Interacting Networks

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β–driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

scholarly journals Dermatopontin interacts with transforming growth factor β and enhances its biological activity

1999 ◽  
Vol 337 (3) ◽  
pp. 537-541 ◽  
Author(s):  
Osamu OKAMOTO ◽  
Sakuhei FUJIWARA ◽  
Mayumi ABE ◽  
Yasufumi SATO
Keyword(s):  
Extracellular Matrix ◽  
Biological Activity ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Inhibitory Activity ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Tgf Β1

Dermatopontin, a recently found low-molecular-mass component of the extracellular matrix, was studied for its interaction with decorin and transforming growth factor β (TGF-β) and its influence on TGF-β bioactivity. Dermatopontin reacted with decorin with an apparent Kd of 100 nM in a solid-phase assay. Dermatopontin inhibited the formation of the decorin–TGF-β1 complex. Decorin also competed with dermatopontin for the binding of this cytokine. The dermatopontin–decorin complex bound 3-fold more TGF-β1 than did each component individually, and binding was inhibited more strongly by decorin preincubated with dermatopontin than by dermatopontin or decorin alone. Dermatopontin augmented the biological activity of TGF-β1, as analysed by the expression of luciferase in mink lung epithelial cells transfected with a plasminogen activator inhibitor–promoter–luciferase construct, although dermatopontin itself did not show apparent induction of luciferase. Dermatopontin showed weak inhibitory activity on the proliferation of mink lung epithelial cells, and it enhanced the growth-inhibitory activity of TGF-β on these cells. Thus dermatopontin increases the cellular response to TGF-β. These findings strongly suggest that dermatopontin modifies the behaviour of TGF-β through interaction with decorin in the microenvironment of the extracellular matrix in vivo.

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